NZ534394A - Process for the manufacture of HMG-CoA reductase inhibitory mevalonic acid derivatives - Google Patents
Process for the manufacture of HMG-CoA reductase inhibitory mevalonic acid derivativesInfo
- Publication number
- NZ534394A NZ534394A NZ534394A NZ53439403A NZ534394A NZ 534394 A NZ534394 A NZ 534394A NZ 534394 A NZ534394 A NZ 534394A NZ 53439403 A NZ53439403 A NZ 53439403A NZ 534394 A NZ534394 A NZ 534394A
- Authority
- NZ
- New Zealand
- Prior art keywords
- formula
- lid
- compound
- phenyl
- residue
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 30
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 21
- KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical class OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 title description 3
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 title description 3
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 title description 3
- 230000002401 inhibitory effect Effects 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 150000002596 lactones Chemical class 0.000 claims abstract description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 125000001931 aliphatic group Chemical group 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- 229920002223 polystyrene Polymers 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 229910052707 ruthenium Inorganic materials 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 229910052703 rhodium Inorganic materials 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 229910052759 nickel Inorganic materials 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims 1
- -1 methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyl-oxy, sec-butyloxy, tert-butyloxy Chemical group 0.000 description 46
- 239000000243 solution Substances 0.000 description 43
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- 239000003054 catalyst Substances 0.000 description 27
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 21
- 239000002904 solvent Substances 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000012442 inert solvent Substances 0.000 description 10
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 10
- 229960002797 pitavastatin Drugs 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 8
- 238000009835 boiling Methods 0.000 description 8
- FJLGEFLZQAZZCD-MCBHFWOFSA-N (3R,5S)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-MCBHFWOFSA-N 0.000 description 7
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 7
- 229940093499 ethyl acetate Drugs 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 229960003765 fluvastatin Drugs 0.000 description 6
- 239000000852 hydrogen donor Substances 0.000 description 6
- 238000009901 transfer hydrogenation reaction Methods 0.000 description 6
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 5
- 239000004793 Polystyrene Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 150000002009 diols Chemical class 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 150000004678 hydrides Chemical class 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- XJSKIUCBAPDUHT-UHFFFAOYSA-N 3-oxo-4-(triphenyl-$l^{5}-phosphanylidene)butanoic acid Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)CC(=O)O)C1=CC=CC=C1 XJSKIUCBAPDUHT-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- 102000004316 Oxidoreductases Human genes 0.000 description 4
- 108090000854 Oxidoreductases Proteins 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 125000003944 tolyl group Chemical group 0.000 description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 3
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 229960005370 atorvastatin Drugs 0.000 description 3
- 159000000007 calcium salts Chemical class 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- FESAXEDIWWXCNG-UHFFFAOYSA-N diethyl(methoxy)borane Chemical compound CCB(CC)OC FESAXEDIWWXCNG-UHFFFAOYSA-N 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- IZZWJPQHPPRVLP-UHFFFAOYSA-N hexane;2-methoxy-2-methylpropane Chemical compound CCCCCC.COC(C)(C)C IZZWJPQHPPRVLP-UHFFFAOYSA-N 0.000 description 3
- 239000011261 inert gas Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 229960002855 simvastatin Drugs 0.000 description 3
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- VXDRHGNOZCFIHZ-UHFFFAOYSA-M (4-ethoxy-3,4-dioxobutyl)-triphenylphosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCC(=O)C(=O)OCC)C1=CC=CC=C1 VXDRHGNOZCFIHZ-UHFFFAOYSA-M 0.000 description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 2
- WWRCMNKATXZARA-UHFFFAOYSA-N 1-Isopropyl-2-methylbenzene Chemical compound CC(C)C1=CC=CC=C1C WWRCMNKATXZARA-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 235000011116 calcium hydroxide Nutrition 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 2
- 229960005110 cerivastatin Drugs 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229930007927 cymene Natural products 0.000 description 2
- 229960004132 diethyl ether Drugs 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- SZQMPNZYYHBKQS-BUHFOSPRSA-N ethyl (e)-5-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3-oxopent-4-enoate Chemical compound C12=CC=CC=C2N(C(C)C)C(/C=C/C(=O)CC(=O)OCC)=C1C1=CC=C(F)C=C1 SZQMPNZYYHBKQS-BUHFOSPRSA-N 0.000 description 2
- UHKATWVCCRPJCX-JKIKYLSZSA-N ethyl (e,3s)-5-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3-hydroxypent-4-enoate Chemical compound C12=CC=CC=C2N(C(C)C)C(/C=C/[C@@H](O)CC(=O)OCC)=C1C1=CC=C(F)C=C1 UHKATWVCCRPJCX-JKIKYLSZSA-N 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229910052741 iridium Inorganic materials 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
- 229960004844 lovastatin Drugs 0.000 description 2
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
- 125000005561 phenanthryl group Chemical group 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 2
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 2
- 229940074439 potassium sodium tartrate Drugs 0.000 description 2
- 229960002965 pravastatin Drugs 0.000 description 2
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000001725 pyrenyl group Chemical group 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 229960000672 rosuvastatin Drugs 0.000 description 2
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 2
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- KBMDBLCFKPRPOC-UHFFFAOYSA-N 2-bromo-3,3,3-trifluoro-2-(trifluoromethyl)propanenitrile Chemical compound FC(F)(F)C(Br)(C#N)C(F)(F)F KBMDBLCFKPRPOC-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- JAHBIRPTCXOGLB-UHFFFAOYSA-N 2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-carbaldehyde Chemical compound C1=CC(F)=CC=C1C1=C(C=O)C(C2CC2)=NC2=CC=CC=C12 JAHBIRPTCXOGLB-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- MMTXSCWTVRMIIY-UHFFFAOYSA-N 3,5-dihydroxyhept-6-enoic acid Chemical group OC(=O)CC(O)CC(O)C=C MMTXSCWTVRMIIY-UHFFFAOYSA-N 0.000 description 1
- PDBMVYIMAMQDCW-UHFFFAOYSA-N 3,5-dihydroxyheptanoic acid Chemical class CCC(O)CC(O)CC(O)=O PDBMVYIMAMQDCW-UHFFFAOYSA-N 0.000 description 1
- NPWWALYZZIFFPB-UHFFFAOYSA-N 3-(4-fluorophenyl)-1-propan-2-ylindole-2-carbaldehyde Chemical compound C12=CC=CC=C2N(C(C)C)C(C=O)=C1C1=CC=C(F)C=C1 NPWWALYZZIFFPB-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- USJRLGNYCQWLPF-UHFFFAOYSA-N chlorophosphane Chemical compound ClP USJRLGNYCQWLPF-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 125000002676 chrysenyl group Chemical group C1(=CC=CC=2C3=CC=C4C=CC=CC4=C3C=CC12)* 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- OHLRLMWUFVDREV-UHFFFAOYSA-N ethyl 4-chloro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)CCl OHLRLMWUFVDREV-UHFFFAOYSA-N 0.000 description 1
- YIXPTDPSXSUMRZ-UHFFFAOYSA-N ethyl 5-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3-hydroxypent-4-enoate Chemical compound CCOC(=O)CC(O)C=CC1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 YIXPTDPSXSUMRZ-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005446 heptyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- YUWFEBAXEOLKSG-UHFFFAOYSA-N hexamethylbenzene Chemical compound CC1=C(C)C(C)=C(C)C(C)=C1C YUWFEBAXEOLKSG-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- YTJXGDYAEOTOCG-UHFFFAOYSA-N lithium;di(propan-2-yl)azanide;oxolane Chemical compound [Li+].C1CCOC1.CC(C)[N-]C(C)C YTJXGDYAEOTOCG-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- AJUXDFHPVZQOGF-UHFFFAOYSA-N n,n-dimethyl-1-naphthylamine Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1 AJUXDFHPVZQOGF-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 125000002080 perylenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC5=CC=CC(C1=C23)=C45)* 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- NUMQCACRALPSHD-UHFFFAOYSA-N tert-Butyl ethyl ether Natural products CCOC(C)(C)C NUMQCACRALPSHD-UHFFFAOYSA-N 0.000 description 1
- RCARMBIYAHBUHR-UQECUQMJSA-N tert-butyl (e,3r,5s)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)(C)OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 RCARMBIYAHBUHR-UQECUQMJSA-N 0.000 description 1
- USGKHYXJISAYPE-PPXNOBOXSA-N tert-butyl (e,3s,5s)-7-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3,5-dihydroxyhept-6-enoate Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@H](O)CC(=O)OC(C)(C)C)=C1C1=CC=C(F)C=C1 USGKHYXJISAYPE-PPXNOBOXSA-N 0.000 description 1
- OZDAOKMCMCEUHP-IBUXMESJSA-N tert-butyl (e,5s)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-5-hydroxy-3-oxohept-6-enoate Chemical compound CC(C)(C)OC(=O)CC(=O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 OZDAOKMCMCEUHP-IBUXMESJSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/535—Organo-phosphoranes
- C07F9/5352—Phosphoranes containing the structure P=C-
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/42—Unsaturated compounds containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/30—Oxygen atoms, e.g. delta-lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0033—Iridium compounds
- C07F15/004—Iridium compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0073—Rhodium compounds
- C07F15/008—Rhodium compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/02—Iron compounds
- C07F15/025—Iron compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/04—Nickel compounds
- C07F15/045—Nickel compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/06—Cobalt compounds
- C07F15/065—Cobalt compounds without a metal-carbon linkage
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Quinoline Compounds (AREA)
- Indole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0204129.1A GB0204129D0 (en) | 2002-02-21 | 2002-02-21 | Process for the manufacture of organic compounds |
PCT/EP2003/001738 WO2003070717A1 (en) | 2002-02-21 | 2003-02-20 | Process for the manufacture of hmg-coa reductase inhibitory mevalonic acid derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
NZ534394A true NZ534394A (en) | 2006-10-27 |
Family
ID=9931523
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NZ534394A NZ534394A (en) | 2002-02-21 | 2003-02-20 | Process for the manufacture of HMG-CoA reductase inhibitory mevalonic acid derivatives |
Country Status (18)
Country | Link |
---|---|
US (3) | US7208623B2 (ja) |
EP (1) | EP1478640A1 (ja) |
JP (1) | JP2005520818A (ja) |
KR (1) | KR100978970B1 (ja) |
CN (1) | CN1318412C (ja) |
AU (1) | AU2003218994B2 (ja) |
BR (1) | BR0307801A (ja) |
CA (1) | CA2473075A1 (ja) |
EC (1) | ECSP045234A (ja) |
GB (1) | GB0204129D0 (ja) |
IL (1) | IL163279A (ja) |
MX (1) | MXPA04008110A (ja) |
NO (1) | NO20043919L (ja) |
NZ (1) | NZ534394A (ja) |
PL (1) | PL370596A1 (ja) |
RU (1) | RU2335500C2 (ja) |
WO (1) | WO2003070717A1 (ja) |
ZA (1) | ZA200405436B (ja) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0204129D0 (en) | 2002-02-21 | 2002-04-10 | Novartis Ag | Process for the manufacture of organic compounds |
PL376557A1 (pl) | 2003-02-12 | 2006-01-09 | Ciba Specialty Chemicals Holding Inc. | Postacie krystaliczne pitawastatyny wapnia |
GB0324791D0 (en) | 2003-10-24 | 2003-11-26 | Astrazeneca Ab | Chemical process |
US20070179166A1 (en) * | 2003-12-24 | 2007-08-02 | Valerie Niddam-Hildesheim | Process for preparation of statins with high syn to anti ratio |
US7851624B2 (en) * | 2003-12-24 | 2010-12-14 | Teva Pharamaceutical Industries Ltd. | Triol form of rosuvastatin and synthesis of rosuvastatin |
EP1634870A1 (en) * | 2004-08-27 | 2006-03-15 | Zhejiang Hisun Pharmaceutical Co. Ltd. | Process and intermediates for the selective synthesis of Fluvastatin |
WO2006035286A2 (en) * | 2004-09-27 | 2006-04-06 | Ranbaxy Laboratories Limited | Process for preparating enantiomerically pure fluvastatin sodium and a novel polymorphic form thereof |
WO2007017117A1 (en) * | 2005-07-28 | 2007-02-15 | Lek Pharmaceuticals D.D. | Process for the synthesis of rosuvastatin calcium |
US8455640B2 (en) | 2006-05-03 | 2013-06-04 | Msn Laboratories Limited | Process for statins and its pharmaceutically acceptable salts thereof |
HUE028475T2 (en) | 2006-10-09 | 2016-12-28 | Msn Laboratories Private Ltd | A novel process for the preparation of statins and their pharmaceutically acceptable salts |
WO2008053334A2 (en) * | 2006-10-31 | 2008-05-08 | Aurobindo Pharma Limited | An improved process for preparing rosuvastatin calcium |
AU2008212622B2 (en) * | 2007-02-08 | 2011-01-27 | Aurobindo Pharma Limited | An improved process for preparation of rosuvastatin calcium |
PL2172471T3 (pl) * | 2007-04-18 | 2013-08-30 | Teva Pharma | Sposób otrzymywania produktów pośrednich inhibitorów reduktazy HMG-CoA |
US7884226B2 (en) * | 2007-07-12 | 2011-02-08 | Teva Pharmaceutical Industries, Ltd. | Purification of rosuvatatin intermediate by thin film evaporation and chemical method |
KR101063146B1 (ko) * | 2008-11-10 | 2011-09-07 | 미래파인켐 주식회사 | 피타바스타틴 중간체의 제조방법 및 이를 이용한 피타바스타틴 헤미 칼슘염의 제조방법 |
EP2387561A4 (en) | 2009-01-19 | 2012-07-25 | Msn Lab Ltd | IMPROVED PROCESS FOR THE PREPARATION OF HIGH-PURITY (3R, 5S) -7-β-CYCLOPROPYL-4- (4-FLUOROPHENYL) QUINOLIN-3-YL-3,5-DIHYDROXY-6 (E) -HEPTENOIC ACID, INCLUDING ITS PHARMACEUTICALLY ACCEPTABLE SALTS |
US8987444B2 (en) | 2010-01-18 | 2015-03-24 | Msn Laboratories Private Limited | Process for the preparation of amide intermediates and their use thereof |
US8912333B2 (en) * | 2010-11-12 | 2014-12-16 | Hetero Research Foundation | Polymorphs of pitavastatin calcium |
FR2970178B1 (fr) | 2011-01-07 | 2014-06-20 | Liliane Therese Jacquot | Promedicaments pour une delivrance specifique au niveau du foie et une meilleure tolerance |
CN103058925B (zh) * | 2011-11-02 | 2015-09-02 | 石药集团中奇制药技术(石家庄)有限公司 | 一种匹伐他汀钙的制备方法 |
TWI516520B (zh) | 2014-10-31 | 2016-01-11 | 財團法人工業技術研究院 | 波長轉換聚合物、其製法及包含其之波長轉換裝置 |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4851427A (en) * | 1985-10-25 | 1989-07-25 | Sandoz Pharm. Corp. | Pyrrole analogs of mevalonolactone, derivatives thereof and pharmaceutical use |
CA1336714C (en) | 1987-08-20 | 1995-08-15 | Yoshihiro Fujikawa | Quinoline type mevalonolactone inhibitors of cholesterol biosynthesis |
FI94339C (fi) * | 1989-07-21 | 1995-08-25 | Warner Lambert Co | Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi |
EP0577040B1 (de) * | 1992-07-02 | 1997-09-24 | Hoechst Aktiengesellschaft | Verfahren zur Herstellung von (3R,5S)6-Hydroxy-3,5-0-isopropyliden-3,5-dihydroxy-hexansäure-tert.-butylester |
US5763688A (en) * | 1994-12-07 | 1998-06-09 | Research Development Corporation Of Japan | Method for producing an alcohol |
DE69635874T2 (de) * | 1995-12-06 | 2006-12-14 | Japan Science And Technology Agency, Kawaguchi | Verfahren zur Herstellung von optisch aktiven Alkoholen |
JP3159661B2 (ja) * | 1997-02-21 | 2001-04-23 | 科学技術振興事業団 | 光学活性アルコール類の製造方法 |
US6187961B1 (en) * | 1997-11-06 | 2001-02-13 | Roche Vitamins Inc. | Process for the preparation of trans-(R,R)-actinol |
JPH11322649A (ja) * | 1998-03-16 | 1999-11-24 | Mitsubishi Chemical Corp | 光学活性アルコールの製造方法 |
JPH11335385A (ja) * | 1998-05-20 | 1999-12-07 | Takasago Internatl Corp | 遷移金属錯体および該錯体を用いた光学活性アルコールの製造方法 |
JP2000212110A (ja) * | 1999-01-27 | 2000-08-02 | Mitsubishi Chemicals Corp | 光学活性α―アルキルベンジルアルコ―ル類の製造方法 |
JP3630002B2 (ja) * | 1999-03-03 | 2005-03-16 | 三菱化学株式会社 | 光学活性1,2−ジオール類の製造方法 |
JP2000327659A (ja) * | 1999-03-15 | 2000-11-28 | Mitsubishi Chemicals Corp | 光学活性ピリジルアルコール類の製造方法 |
US6603015B2 (en) * | 1999-03-29 | 2003-08-05 | University Of Kansas | Synthesis of epothilones |
US6211412B1 (en) * | 1999-03-29 | 2001-04-03 | The University Of Kansas | Synthesis of epothilones |
JP2001104795A (ja) * | 1999-10-13 | 2001-04-17 | Mitsubishi Chemicals Corp | ルテニウム触媒組成物 |
JP3720235B2 (ja) * | 2000-03-14 | 2005-11-24 | 高砂香料工業株式会社 | 光学活性ルテニウムホスフィン錯体の製造方法及び該錯体を用いた光学活性アルコールの製造方法 |
EP1136475B1 (en) * | 2000-03-22 | 2004-08-18 | F. Hoffmann-La Roche Ag | Piperidine and piperazine compounds for use in the treatment of Alzheimer |
US6743926B2 (en) * | 2000-05-26 | 2004-06-01 | Ciba Specialty Chemicals Corporation | Process for the preparation of indole derivatives and intermediates of the process |
JP2004504371A (ja) * | 2000-07-24 | 2004-02-12 | カイロテック・テクノロジー・リミテッド | ルテニウム錯体および不斉水素化におけるその使用 |
GB0204129D0 (en) | 2002-02-21 | 2002-04-10 | Novartis Ag | Process for the manufacture of organic compounds |
-
2002
- 2002-02-21 GB GBGB0204129.1A patent/GB0204129D0/en not_active Ceased
-
2003
- 2003-02-20 WO PCT/EP2003/001738 patent/WO2003070717A1/en active IP Right Grant
- 2003-02-20 RU RU2004128256/04A patent/RU2335500C2/ru not_active IP Right Cessation
- 2003-02-20 CN CNB038042886A patent/CN1318412C/zh not_active Expired - Fee Related
- 2003-02-20 US US10/504,655 patent/US7208623B2/en not_active Expired - Fee Related
- 2003-02-20 NZ NZ534394A patent/NZ534394A/en not_active IP Right Cessation
- 2003-02-20 BR BR0307801-9A patent/BR0307801A/pt not_active IP Right Cessation
- 2003-02-20 CA CA002473075A patent/CA2473075A1/en not_active Abandoned
- 2003-02-20 JP JP2003569624A patent/JP2005520818A/ja active Pending
- 2003-02-20 AU AU2003218994A patent/AU2003218994B2/en not_active Ceased
- 2003-02-20 MX MXPA04008110A patent/MXPA04008110A/es active IP Right Grant
- 2003-02-20 PL PL03370596A patent/PL370596A1/xx not_active Application Discontinuation
- 2003-02-20 KR KR1020047013033A patent/KR100978970B1/ko not_active IP Right Cessation
- 2003-02-20 EP EP03714750A patent/EP1478640A1/en not_active Withdrawn
-
2004
- 2004-07-08 ZA ZA200405436A patent/ZA200405436B/en unknown
- 2004-07-29 IL IL163279A patent/IL163279A/en not_active IP Right Cessation
- 2004-08-16 EC EC2004005234A patent/ECSP045234A/es unknown
- 2004-09-20 NO NO20043919A patent/NO20043919L/no not_active Application Discontinuation
-
2007
- 2007-03-09 US US11/684,134 patent/US20070155970A1/en not_active Abandoned
-
2008
- 2008-07-23 US US12/220,259 patent/US20080312462A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
GB0204129D0 (en) | 2002-04-10 |
PL370596A1 (en) | 2005-05-30 |
JP2005520818A (ja) | 2005-07-14 |
RU2335500C2 (ru) | 2008-10-10 |
US7208623B2 (en) | 2007-04-24 |
US20050159480A1 (en) | 2005-07-21 |
US20070155970A1 (en) | 2007-07-05 |
KR100978970B1 (ko) | 2010-08-30 |
RU2004128256A (ru) | 2005-06-27 |
KR20040111360A (ko) | 2004-12-31 |
US20080312462A1 (en) | 2008-12-18 |
NO20043919L (no) | 2004-09-20 |
BR0307801A (pt) | 2004-12-21 |
WO2003070717A1 (en) | 2003-08-28 |
ZA200405436B (en) | 2005-06-17 |
MXPA04008110A (es) | 2004-11-26 |
ECSP045234A (es) | 2004-09-28 |
AU2003218994A1 (en) | 2003-09-09 |
IL163279A (en) | 2010-06-30 |
AU2003218994B2 (en) | 2007-08-09 |
CA2473075A1 (en) | 2003-08-23 |
EP1478640A1 (en) | 2004-11-24 |
CN1318412C (zh) | 2007-05-30 |
CN1636004A (zh) | 2005-07-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20070155970A1 (en) | Process for the manufacture of hmg-coa reductase inhibitory mevalonic acid derivatives | |
CN108546238B (zh) | α-酮酰胺类化合物的不对称氢化方法 | |
US8889865B2 (en) | Process for preparing amines from alcohols and ammonia | |
Kisanga et al. | Synthesis of new proazaphosphatranes and their application in organic synthesis | |
US6909003B2 (en) | Process for the manufacture of organic compounds | |
JP6504530B2 (ja) | 光学活性な2−(2−フルオロビフェニル−4−イル)プロパン酸の製造法 | |
CA2696195A1 (en) | Process for preparing pyrimidine derivatives | |
JP5089634B2 (ja) | アルカリ土類金属系触媒、及び反応方法 | |
JP5622019B2 (ja) | アミノアルコール誘導体塩構造を有する不斉有機分子触媒及び該不斉有機分子触媒を用いた光学活性化合物の製造方法 | |
JP4050294B2 (ja) | 光学活性コバルト(ii)錯体 | |
CN112028874A (zh) | 艾立替尼的合成方法 | |
JP2010229097A (ja) | 新規オキサゾリジン誘導体及び新規オキサゾリジン誘導体塩、並びに該オキサゾリジン誘導体塩を不斉有機分子触媒とした光学活性化合物の製造方法 | |
WO2006083030A1 (ja) | 脂肪酸の製造方法および脂肪酸の塩結晶 | |
JPH09151143A (ja) | 新規な光学活性コバルト(ii)錯体および光学活性アルコールの製造方法 | |
CN113943220B (zh) | 一种1,4-二羰基化合物类衍生物的光化学合成方法 | |
JPH08310981A (ja) | 光学活性アルコールの製造方法 | |
KR102500243B1 (ko) | 5-(c1~c4 알킬) 테트라졸의 합성방법 | |
KR100619117B1 (ko) | 시스-시클로프로판-감마-부티로락톤 화합물 및 그의제조방법 | |
JP2006151839A (ja) | α,β−不飽和カルボン酸誘導体からのエナンチオ選択的β−シアノカルボン酸誘導体の調製方法、及び該方法に用いる触媒 | |
JP2946678B2 (ja) | キラルなフェロセン誘導体 | |
JP5246903B2 (ja) | β−アミノカルボニル化合物の製法 | |
JPH05306291A (ja) | 光学活性ジホスフィノカルボン酸誘導体 | |
JP2000273062A (ja) | ハイドロキノン類の製造方法 | |
WO2010098193A1 (ja) | β-アミノカルボニル化合物の製法及びリチウムビナフトラート錯体 | |
WO2003031425A1 (en) | Diastereomerically or enantiomerically selective lactonisation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PSEA | Patent sealed | ||
RENW | Renewal (renewal fees accepted) | ||
RENW | Renewal (renewal fees accepted) | ||
LAPS | Patent lapsed |